The A148T variant of the CDKN2A gene is not associated with melanoma risk in the French and Italian populations.
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Biomedical subjects
Publications and source records attributed to Ketty Peris.
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Several reviews and guidelines on the management of mycosis fungoides and Sézary syndrome (MF/SS) have been published; however, treatment strategies for patients with MF/SS vary from institution to institution and no European consensus has yet been established. There are few phase III trials to support treatment decisions for MF/SS and treatment is often determined by institutional experience. In order to summarise the available evidence and review 'best practices' from each national group, the European Organisation for Research and Treatment of Cancer (EORTC) Cutaneous Lymphoma Task Force met in September 2004 to establish European guidelines for the treatment of MF/SS. This article reviews the treatment regimens selected for inclusion in the guidelines and summarises the clinical data for treatments appropriate for each stage of MF/SS. Guideline recommendations are presented according to the quality of supporting data, as defined by the Oxford Centre for Evidence-Based Medicine. Skin-directed therapies are the most appropriate option for early-stage MF/SS and most patients can look forward to a normal life expectancy. Patients with advanced disease should be encouraged to participate in clinical trials and maintenance of quality of life should be paramount.
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OBJECTIVE: To investigate the dermoscopic features of acral melanocytic lesions in a white population in central Italy. DESIGN: Retrospective review. SETTING: University dermatology department. PATIENTS: Six hundred fifty-one Italian subjects, ranging in age from 6 months to 78 years. MAIN OUTCOME MEASURES: We retrospectively investigated all digital dermoscopic images of acral melanocytic lesions included in our database from January 1996 to May 2005. RESULTS: We retrieved digital images of 723 benign acral melanocytic lesions in 641 patients (235 males and 406 females; mean age, 26.5 years) and of 10 acral melanomas in 10 patients (7 males and 3 females; mean age, 65 years). Individual lesions were located on the soles (n=520), fingers (n=146), and palms (n=67). Among acral nevi, the parallel furrow (42.1%) was the most common pattern, followed by the latticelike (14.9%), nontypical (13.7%), fibrillar (10.8%), homogeneous (9.3%), globular (5.4%), and reticular (2.1%) patterns. The frequency of distribution of the latticelike, nontypical, fibrillar, and homogeneous patterns significantly differed (P<.001, P=.03, P<.001, and P=.03, respectively) between anatomical sites. Also, 13 acral nevi (1.8%), mainly located on the fingers, showed a new combined pattern (transition pattern) consisting of a brownish black network associated with a parallel furrow or latticelike pattern. All 10 acral melanomas showed a multicomponent dermoscopic pattern. CONCLUSIONS: In our series of acral nevi, we observed 8 dermoscopic patterns, with varying distribution by anatomical site. Identification of a specific pattern is highly suggestive of the benign or the malignant nature of any given acral melanocytic lesion.
BACKGROUND: Imiquimod has been successfully used for treatment of various epithelial cutaneous neoplasms. OBJECTIVE: Our aim was to evaluate the efficacy and tolerability of imiquimod 5% cream for treatment of Bowen's disease and invasive squamous cell carcinoma (SCC) in patients who were unsuitable candidates for surgery. METHOD: Five Bowen's disease lesions and 7 invasive SCC lesions on 10 patients were treated with imiquimod once daily 5 times a week for a maximum of 16 weeks. RESULTS: After 8 to 12 weeks of treatment, 4 of 5 Bowen's disease lesions (80%) and 5 of 7 invasive SCCs (71.4%) showed complete clinicopathologic regression. The remaining 3 lesions showed partial regression after 16 weeks of treatment. No recurrence has been detected after a follow-up period of 24 to 38 months (mean, 31 months). LIMITATIONS: The study is an open-label clinical trial on a small number of selected patients, with lack of excision with serial step sections. CONCLUSION: Topical application of imiquimod 5% cream might represent an alternative topical treatment to surgery in selected cases of Bowen's disease and invasive SCC.
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The melanocortin-1 receptor (MC1R) gene is a key determinant of the physiological variation in human skin pigmentation. It is highly polymorphic, and specific MC1R allelic variants have been shown to be low-penetrance melanoma susceptibility alleles. We investigated the contribution of the MC1R genotype to the risk of sporadic cutaneous melanoma in a population in central Italy. One hundred patients with sporadic cutaneous melanoma of any stage and 100 unrelated control individuals were consecutively recruited between 1 September 2000 and 31 December 2001. Information on ethnic background and residential history, phenotypic risk factors for melanoma and ultraviolet exposure habits was collected through a standardized questionnaire and total skin examination. Sequence analysis of the entire coding region of the MC1R gene was performed. A total of 26 MC1R variants, including a novel 123_124insT allele, was identified in our population, with the most frequent allele being V60L. Carriers of high-penetrance 'R' MC1R alleles, that define MC1R variants strongly associated with the red hair colour phenotype, showed a statistically significant increase in melanoma risk [odds ratio (OR), 2.55; 95% confidence interval (CI), 1.19-5.55]. No significant association with melanoma risk was observed for carriers of 'r' variants (OR, 0.90; 95% CI, 0.45-1.82). Amongst individual MC1R variants, the R151C allele was significantly associated with melanoma, with an OR of 2.94 (95% CI, 1.04-8.31). After stratification for clinical and ultraviolet exposure risk factors, the melanoma risk associated with high-penetrance 'R' variants appeared to increase significantly, mainly in the presence of clinically atypical naevi, more than 50 melanocytic naevi, high recreational sun exposure and occupational sun exposure. These results support the contribution of high-penetrance MC1R variant alleles to genetic predisposition to sporadic cutaneous melanoma in a population in central Italy.
The combined nevus is a clinical simulator of melanoma, and clinical examination alone can be inadequate to diagnose this melanocytic pigmented skin lesion. Dermoscopy is a useful tool to differentiate the features related to each type of nevus. We report two cases of combined nevi dermoscopically characterized by a diffuse blue-whitish pigmentation similar to the blue-whitish veil, suggesting the diagnosis of melanoma.
BACKGROUND: Hypoepiluminescence microscopy (HELM) is a new dermoscopic approach for analysis of pigmented skin lesions (PSLs) after surgical excision. OBJECTIVES: The objective was to verify whether this method could provide additional morphologic information for diagnostic or didactic purposes compared to conventional epiluminescence microscopy (ELM). PATIENTS AND METHODS: Thirty-one PSLs from 30 patients were consecutively evaluated by ELM and, after excision, by HELM. For HELM examination, the lesion was positioned on a glass slide and illuminated from above with a halogen lamp and from underneath with an LED source. All lesions were subsequently examined histopathologically. RESULTS: In 11 of 31 (35.5%) lesions, a typical pigment network, as assessed by ELM, appeared bidimensional with HELM. In 9 lesions (9/31; 29%) ELM showed a gray-blue area, while HELM allowed us to distinguish 5 lesions (5/9, 55.5%) with gray area predominant showing a lichenoid lymphocytic infiltration and few melanophages from the other 4 lesions (4/9, 44,5%) with heavy dermal accumulation of pigmented melanocytes or melanophages where a blue area was clearly visible at HELM. In 9 other cases (29%), ELM analysis revealed a central homogeneous dark brown/black pigmentation that in 7 cases was seen under HELM examination to consist of globules. CONCLUSIONS: HELM is particularly useful in evaluating heavily PSLs or structures located in the reticular dermis.
BACKGROUND: We present the results of a multicentre, not controlled, clinical study on the tolerability and efficacy of tazarotene gel, used as short contact therapy (SCT), in psoriasis vulgaris. OBJECTIVE: To evaluate whether irritant contact dermatitis caused by tazarotene was less frequent and/or less severe with SCT than with traditional therapy, and whether SCT with tazarotene was as effective as traditional therapy. METHODS: Forty-three patients with plaque psoriasis were treated by SCT with 0.1% tazarotene gel (once daily application for 20 min, followed by washing with water). Treatment duration was 45 days. RESULTS: Irritant contact dermatitis caused by tazarotene used as SCT was much less frequent and severe than traditional treatment with the same drug. SCT with tazarotene was effective in the treatment of plaque psoriasis. CONCLUSION: Tazarotene, used as SCT, was better tolerated than the same drug used as traditional treatment. Furthermore, SCT appeared to be as effective as traditional therapy with the same drug.
The aim of this review is to report the current understanding of the molecular genetics of melanoma predisposition. To date, two high-penetrance melanoma susceptibility genes, cyclin-dependent kinas inhibitor (CDKN)2A on chromosome 9p21 and cyclin-dependent kinase (CDK4) on 12q13, have been identified. Germline inactivating mutations of the CDKN2A gene are the most common cause of inherited susceptibility to melanoma. Worldwide, a few families have been found to harbor CDK4 mutations. However, predisposing alterations to familial melanoma are still unknown in a large proportion of kindreds. Other melanoma susceptibility loci have been mapped through genome-wide linkage analysis, although the putative causal genes at these loci have yet to be identified. Much ongoing research is being focused on the identification of low-penetrance melanoma susceptibility genes that confer a lower melanoma risk with more frequent variations. Specific variants of the MC1R gene have been demonstrated to confer an increase in melanoma risk. In addition, conflicting data are available on other potential low-penetrance genes encoding proteins involved in pigmentation, cell growth and differentiation, DNA repair or detoxifying of metabolites.
Chronic exposure to ultraviolet (UV) radiation causes skin cancer in humans and mice. We have previously shown that in hairless SKH-hr1 mice, UVB-induced p53 mutations arise very early, well before tumor development. In this study, we investigated whether discontinuation of UVB exposure before the onset of skin tumors results in the disappearance of p53 mutations in the skin of hairless SKH-hr1 mice. Irradiation of mice at a dose of 2.5 kJ/m2 three times a week for 8 weeks induced p53 mutations in the epidermal keratinocytes of 100% of the mice. UVB irradiation was discontinued after 8 weeks, but p53 mutations at most hotspot codons were still present even 22 weeks later. During that period, the percent of mice carrying p53(V154A/R155C), p53(H175H/H176Y), and p53R275C mutant alleles remained at or near 100%, whereas the percentage of mice with p53R270C mutation decreased by 45%. As expected, discontinuation of UVB after 8 weeks resulted in a delay in tumor development. A 100% of tumors carried p53(V154A/R155C) mutant alleles, 76% carried p53(H175H/H176Y) mutants, and 24 and 19% carried p53R270C and p53R275C mutants, respectively. These results suggest that different UVB-induced p53 mutants may provide different survival advantages to keratinocytes in the absence of further UVB exposure and that skin cancer development can be delayed but not prevented by avoidance of further exposure to UVB radiation.
OBJECTIVE: To achieve a clinicopathologic classification of Spitz nevi by comparing their clinical, dermoscopic, and histopathologic features. DESIGN: Eighty-three cases were independently reviewed by 3 histopathologists and preliminarily classified into classic or desmoplastic Spitz nevus (CDSN, n = 11), pigmented Spitz nevus (PSN, n = 14), Reed nevus (RN, n = 16), or atypical Spitz nevus (ASN, n = 14); the remaining 28 cases were then placed into an intermediate category (pigmented Spitz-Reed nevus, PSRN) because a unanimous diagnosis of either PSN or RN was not reached. SETTING: University dermatology and pathology departments and general hospital pathology departments. PATIENTS: A sample of subjects with excised melanocytic lesions. MAIN OUTCOME MEASURE: Frequency of dermoscopic patterns within the different histopathologic subtypes of Spitz nevi. RESULTS: Overlapping clinical, dermoscopic, and histopathologic findings were observed among PSN, RN, and PSRN, thereby justifying their inclusion into the single PSRN diagnostic category. Asymmetry was the most frequent indicator of histopathologic ASN (79%; n = 11); in only 4 cases did dermoscopic asymmetry show no histopathologic counterpart, and in those cases the discrepancy was probably the result of an artifact of the gross sampling technique carried out with no attention to the dermoscopic features. CONCLUSIONS: Among Spitz nevi, histopathologic distinction between PSN and RN is difficult, not reproducible, and may be clinically useless. A simple clinicopathologic classification of these neoplasms might therefore be structured as CDSN, PSRN, and ASN. Asymmetry should be assessed using both dermoscopic and histopathologic analysis, and reliability in histopathologic diagnosis may be enhanced by the simultaneous evaluation of the corresponding dermoscopic images.
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